This K23 award will provide Corinne Keet, MD, MS, with the necessary training and experience to become an independent investigator performing patient-oriented research in the field of allergy and immunology. In this proposal, Dr. Keet will study key environmental and genetic risk factors for food allergy (FA), a common disease with largely unknown environmental and genetic determinants. Although it has long been observed that eczema tends to lead to FA, why this is the case is unknown. Previous work by Dr. Keet suggested that UV light and vitamin D may alter this relationship, by showing that eczema and fall birth interacted to increase the risk of FA. Here, Dr. Keet will explore the role of susceptiblity to skin barrier impairment in FA, how it may interact with fall birth, and how the vitamin D pathway may play a role in FA. Specifically, Dr. Keet will test the hypotheses that genetic predisposition to skin barrier dysfunction increases risk of FA, that this may be modified by fall birth, and that fall birth increases the risk of skin barrier dysfunction (Aim 1), and the hypothess that the vitamin D pathway is associated with FA, interacts with fall birth, and that fall birth leds to decreased vitamin D in early life (Aim 2). To accomplish these aims, Dr. Keet will use both an already established large family-based cohort of food allergic patients and a new cohort of 3 month old infants. Dr. Keet has assembled a mentorship team with deep and diverse expertise. Dr. Xiaobin Wang, the primary mentor, brings deep expertise in the study of early childhood determinants of disease, the establishment and maintenance of cohorts, and has a strong track record of mentoring young investigators for successful careers in academic medicine. Dr. Robert Wood brings expertise in pediatric allergy, in addition to extensive experience in clinical research. Dr. Terri Beaty is an expert in genetic epidemiology, and Dr. Ingo Ruczinski specializes in the analysis of genomic studies. All of these mentors have pledged their time, resources and expertise to facilitate Dr. Keet's career development. This K23 award will also provide Dr. Keet with opportunities for advanced training in epidemiology, including the completion of a PhD in Epidemiology at the Johns Hopkins Bloomberg School of Public Health (JHBSPH), which will be essential to the success of this project and to her future success in patient-oriented research of the early life determinants of allergic disease. The candidate's past experiences illustrate her commitment to a career in academic medicine and ability to be successful in this field. During medical school, she completed a Masters focusing on epidemiology. She then completed pediatric residency and a fellowship in Pediatric Allergy and Immunology at Johns Hopkins. Under the mentorship of Dr. Wood, during fellowship she conducted a clinical trial of immunotherapy for milk allergy, demonstrating that oral immunotherapy was more effective that sublingual, and that desensitization achieved over 2 years of treatment could be rapidly lost. During this time she also became interested in broader questions related to the development of allergic disease, and when she joined the faculty at Johns Hopkins as an Assistant Professor of Pediatrics in 2010, she enrolled in a PhD program in Epidemiology at the JHBSPH. Since that time, she has been supported by a KL2 award as a clinical research scholar, and has completed rigorous coursework in epidemiology, biostatistics and genetic epidemiology, while starting research projects on the national epidemiology of allergic disease. The current proposal builds on these experiences with additional mentorship to establish Dr. Keet as an expert in the epidemiology of allergic diseases, including genetic epidemiology of these diseases. With training in clinical research, epidemiology and allergy/immunology, the candidate is uniquely positioned to conduct these studies. The training described here, and the data generated, will provide a foundation needed to compete for a R01 grant from the NIH and establish an independent career as an expert in the early childhood determinants of allergic disease. Relevance: FA affects approximately 5% of children in the U.S., but the causes are largely unknown. The results of this work may inform strategies to prevent FA. The goals of this K23 award are to provide a training platform for Corinne Keet, MD, MS to become an independent investigator performing patient-oriented research in the field of allergy and immunology, and to explore the mechanisms of the development of food allergy, a disease that affects approximately 5% of children. In two pediatric cohorts, we will examine (1) two candidate gene pathways for food allergy, the skin barrier and vitamin D, (2) interactions between these pathways and season of birth, and (3) the effects of season of birth on early life skin barrier and vitamin D. The findings from this study may inform preventative strategies for food allergy.